Studies have continued to determine the molecular and cellular targets of estrogenic chemicals and establish the mechanisms by which interactions of estrogens with developing genital tract target cells result in permanently altered differentiation, including dysmorphology and neoplasia. In the developmentally-estrogenized mouse, neoplasias in the female structures derived from the Mullerian duct (e.g., uterus) were demonstrated. Hormone-dependent gene expression (uterine lactoferrin, TGF-alpha, or EGF) was shown to be persistently expressed in the absence of further estrogen. The developing Mullerian duct has been further studied at the cellular and molecular levels. It was determined that, in the immature mouse uterus, the epithelium was relatively deficient in detectable estrogen receptor (ER) although the mitogenic signal of estrogen is apparently transduced in ER-deficient epithelial cells. EGF stimulates uterine cell division in the developing reproductive tract and growth factors may play a role in both the growth and differentiation of these tissues. In fact, the ER may be protective for estrogen-associated neoplastic transformation in estrogen target tissues, Studies on phospholipid turnover, especially phosphoinositides (PI), may provide further insights into signal transduction mechanisms associated with estrogens, since both estrogen and EGF induce similar patterns of PI metabolism. The growth characteristics of murine uterine epithelium and stroma were compared in serum-free tissue culture. Also, the expression of uterine lactoferrin, a gene which requires estrogen for its expression in vivo, was studied in cell culture and found to be constitutive. These studies together support a complex developmental progression in hormone responsiveness in the female genital tract with important clues for neoplasia.